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Last update 08 May 2025

PDE1A

Last update 08 May 2025

Basic Info

Synonyms

61 kDa Cam-PDE, Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A, Cam-PDE 1A

+ [5]

Introduction

Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP.

Drugs associated with PDE1A

PDE-1 inhibitors(Boehringer Ingelheim)

Target

PDE1A

Mechanism

PDE1A inhibitors

Active Org.

Boehringer Ingelheim International GmbH

Originator Org.

Boehringer Ingelheim International GmbH

Active Indication

Schizophrenia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PDE1A

100 Translational Medicine associated with PDE1A

0 Patents (Medical) associated with PDE1A

135

Literatures (Medical) associated with PDE1A

01 May 2025·BJU International

Inhibition of phosphodiesterases 1 and 4 prevents myofibroblast transformation in Peyronie's disease

Article

Author: Ralph, David J. ; Bustin, Stephen A. ; Ilg, Marcus M. ; Cellek, Selim ; Harding, Sophie L.

ObjectivesTo investigate which phosphodiesterase (PDE) isoforms are expressed in fibroblasts isolated from the tunica albuginea (TA) of patients with Peyronie's disease (PD), and to measure the potency of PDE inhibitors in preventing transformation of these fibroblasts to profibrotic myofibroblasts.Materials and MethodsFibroblasts isolated from the TA of men undergoing surgery for correction of PD curvature were transformed to myofibroblasts using transforming growth factor beta‐1. The expression of 21 PDE isoforms was investigated using quantitative reverse transcriptase‐polymerase chain reaction and protein analysis, as were the effects of various PDE inhibitors on prevention of myofibroblast transformation. Intracellular cAMP and cGMP in the presence of PDE inhibitors were quantified using cGMP/cAMP enzyme‐linked immunosorbant assay assays.ResultsWe found that PDE1A, 1C, 4, 5A, 7B and 8B were expressed at mRNA and protein levels. Selective inhibitors of these enzymes prevented myofibroblast transformation in a concentration‐dependent manner, with PDE1 inhibitor ITI‐214 and PDE4 inhibitors roflumilast and roflumilast N‐oxide showing greatest potency. ITI‐214 and roflumilast N‐oxide increased intracellular cAMP, but not cGMP, in a concentration‐dependent manner.ConclusionsThis is the first demonstration of the expression of PDE1, 7 and 8 isoforms, and the function of PDE1 and PDE4 in human TA fibroblasts. The ability of inhibitors of these enzymes to prevent myofibroblast transformation suggests that such inhibitors can be developed to treat acute PD.

01 Mar 2025·British Journal of Pharmacology

Cross‐pathway integration of cAMP signals through cGMP and calcium‐regulated phosphodiesterases in mouse striatal cholinergic interneurons

Article

Author: Bompierre, Ségolène ; Lefevre, Marion ; Kehler, Jan ; Pumo, Anna ; Byelyayeva, Yelyzaveta ; Mota, Elia ; Vincent, Pierre ; Castro, Liliana R. V.

AbstractBackground and PurposeAcetylcholine plays a key role in striatal function. Firing properties of striatal cholinergic interneurons depend on intracellular cAMP through the regulation of Ih currents. Yet, the dynamics of cyclic nucleotide signalling in these neurons have remained elusive.Experimental approachWe used highly selective FRET biosensors and pharmacological compounds to analyse the functional contribution of phosphodiesterases in striatal cholinergic interneurons in mouse brain slices.Key ResultsPDE1A, PDE3A and PDE4 appear as the main controllers of cAMP levels in striatal cholinergic interneurons. The calcium signal elicited through NMDA or metabotropic glutamate receptors activates PDE1A, which degrades both cAMP and cGMP. Interestingly, the nitric oxide/cGMP pathway amplifies cAMP signalling via PDE3A inhibition—a mechanism hitherto unexplored in a neuronal context.Conclusions and ImplicationsThe expression pattern of specific PDE enzymes in striatal cholinergic interneurons, by integrating diverse intracellular pathways, can adjust cAMP responses bidirectionally. These properties eventually allow striatal cholinergic interneurons to dynamically regulate their overall activity and modulate acetylcholine release. Remarkably, this effect is the opposite of the cGMP‐induced inhibition of cAMP signals involving PDE2A in striatal medium‐sized spiny neurons, which provides important insights for the understanding of signal integration in the striatum.

01 Dec 2024·Alzheimer's & Dementia

On the Risk of Alzheimer’s Disease in Survivors of Myocardial Infarction: A Mendelian Randomization Study

Article

Author: Zhang, Yian ; Ashebir, Yibeltal Arega ; Shao, Yongzhao

AbstractBackgroundMyocardial infarction (MI) is a leading cause of death while those surviving MI are still at risk of developing dementias. Alzheimer’s disease (AD) is the leading cause of dementia currently without a cure or an effective prevention even in vulnerable subpopulations. Both AD and MI are common causes of disabilities and deaths in aging populations. It is of interest to investigate AD risk and possible preventive measures for AD among vulnerable aging populations including those surviving MI (survMI).MethodEmploying a two‐sample Mendelian randomization (2SMR) analysis, we assessed the causal relationship between survMI and the risk of AD, utilizing independent AD and MI genome‐wide association study (GWAS) summary datasets. Sensitivity tests, including MR‐Egger intercept test, Cochran Q‐test, and leave‐one‐out analysis, were performed to ensure robustness.ResultThe 2SMR study, utilizing 62 independent single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), revealed a decreased risk of AD associated with survMI (OR = 0.897, p = 6.03E‐11). The MR‐Egger intercept test (p = 0.405) indicated the absence of horizontal pleiotropy, and no evidence of heterogeneity was observed based on the Cochran Q‐test (p = 0.429). Some of the instrumental genetic variants, rs765549, rs11652894, rs12693302, and rs10455872 are linked to LPL, SREBF1, PDE1A, and SLC22A3 genes—targets of medicines and dietary supplements like calcium channel blockers and Omega‐3/fish oil commonly used to enhance MI survival chances.ConclusionThe 2SMR analysis indicated a significant causal association between survMI and a reduced risk of AD. This suggests that commonly‐used medications, including calcium channel blockers, and supplements like Omega‐3 products, may contribute to lowering the risk of AD. Further studies are essential to validate these findings and explore potential preventive measures for AD using combinations of medications and dietary supplements commonly employed to enhance the probability of surviving MI.

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PDE1A

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